A monoclonal gammopathy is a common finding in the general practitioner’s office. An active search for a paraproteinemia is indicated in case of suspected malignancy, evidence of end organ damage (e.g. anemia, renal insufficiency) or in case of recurrent infections or prolonged fatigue. Plasma cell myeloma is an important differential diagnosis of a monoclonal gammopathy and implies a broad spectrum of diagnostic as well as therapeutic consequences for the patient. Plasma cell myeloma is still being considered an incurable disease, but its prognosis could be significantly improved with the introduction of new drugs.